While recent headlines blared that an FDA panel had voted to keep COX-2 drugs on the market, the sense of what this panel actually did was difficult to get from most news reports.
The panel, consisting of the the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee, officially recognized the cardiovascular risks associated with COX-2 selective pain relievers such as rofecoxib (Vioxx) and celecoxib (Celebrex). At the same time, the panel supported the continued marketing of these drugs, but only in combination with "black box" warning labels, lower doses, a halt to direct-to-consumer advertising, better doctor and patient education, and better post-marketing surveillance.
The COX-2 drugs are non-steroidal antiinflammatory drugs (NSAIDs) that, compared with other NSAIDS, cause fewer gastrointestinal side effects. While there have been indications for several years that the COX -2 drugs increase the risk of heart attack and stroke, this increased risk was proven only recently. When Merck finally (and belatedly, many say) withdrew Vioxx from the market in the fall of 2004, a storm of controversy arose about ALL the COX-2 drugs.
To quell the storm, the FDA panel was assembled in February, 2005. After reviewing all the available evidence, the panel overwhelmingly agreed that COX-2 drugs carry an increased risk of cardiovascular side effects. But since pain can be a disabling symptom, and since some patients have no other good alternative for relieving pain, the panel also said these drugs should continue to be made available. Specifically, they recommended the following:
Celecoxib (Celebrex, Pfizer): The panel decided that celecoxib should continue to be available (with appropriate warning labels and marketing changes) but that doses should be kept down to 200 mg.
Rofecoxib (Vioxx, Merck): By a narrow margin (17 to 15) the panel recommended that rofecoxib should again be marketed. While rofecoxib was found to be substantially riskier than other COX-2 drugs, the panel noted that this is the only COX-2 drug available to treat juvenile rheumatoid arthritis, and the only one that can be taken by patients allergic to sulfonamides. The panel recommended eliminating the 50 mg dose of this drug, and reducing the standard dose from 25 mg to 12.5 mg. Whether Merck will begin selling rofecoxib again remains to be seen.
Valdecoxib (Bextra, Pfizer) The committee narrowly voted to allow the continued availability of this drug, noting that there is little data to support its use, and worrying that there are next to no long-term data on its side effects.
DrRich Comments:
Clearly, the FDA panel felt it was wrong to withhold COX-2 drugs from patients who really need them. But patients should be given these drugs only when necessary, and only after all the risks have been fully explained to them.
Specifically, COX-2 drugs should be used only in patients who a) have significant pain that needs to be treated, b) cannot tolerate other NSAIDs due to GI side effects, and c) are felt to have a low underlying risk of heart attack and stroke.
Further, if a COX-2 is to be used, celecoxib should normally be the drug of choice. Rofecoxib (if Merck decides to sell it again) should be reserved for patients allergic to sulfonamides. Valdecoxib probably should be avoided altogether until more data is available on its long-term effects.
Finally, as has become customary after expert panels make controversial recommendations, the press was happy to point out that almost one-third of the panel members had recent ties to the pharmaceutical industry. Given that most medical research is funded by industry, however, DrRich is most impressed that two-thirds of the experts recruited to the panel by the FDA had managed to become experts without industral support.
